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1.
Microsc Res Tech ; 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37129001

RESUMO

Ferroptosis is a newly defined form of cell death involved in neurologic disease. Resveratrol is a non-flavonoid polyphenolic compound with anti-inflammatory and antioxidant properties, but its potential therapeutic mechanism in spinal cord injury (SCI) remains unknown. Therefore, this study evaluates the mechanism by which resveratrol promotes neurological and motor function recovery in mice with SCI. The motor function of mice was evaluated using the Basso Mouse Scale score and footprint test. The effect of resveratrol on the neuronal cell state was observed using NeuN, fluoro-Jade C, and Nissl staining. The expression of iron content in injured segments was observed using Perls blue and Diaminobenzidine staining. The effect of resveratrol on the levels of malondialdehyde, glutathione, Fe2+ , and glutathione peroxidase 4 enzyme activity was also investigated. The mitochondrial ultrastructures of injured segment cells were observed using transmission electron microscope, while the protein levels of ferroptosis-related targets were detected using Western blot. Our findings show that resveratrol improves motor function after SCI and has certain neuroprotective effects; in ferroptosis-related studies, resveratrol inhibited the expression of ferroptosis-related proteins and ions. Resveratrol improved changes in mitochondrial morphology. Mechanistically, the Nrf2 inhibitor ML385 reversed the inhibitory effect of resveratrol on ferroptosis-related genes, indicating that resveratrol inhibits ferroptosis through the Nrf2/GPX4 pathway. Our findings elucidate that resveratrol promotes functional recovery, inhibits ferroptosis post-SCI, and provides an experimental basis for subsequent clinical translational research.

2.
Health Phys ; 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37195193

RESUMO

ABSTRACT: This study investigated the amount and duration of water consumption in neuroendocrine tumor patients after receiving 177Lu-DOTATATE radionuclide therapy. We recruited 39 patients with neuroendocrine tumors, all of whom were treated with 177Lu-DOTATATE radionuclide while in the nuclear medicine ward of a tertiary hospital in Nanjing from January 2021 to April 2022. We conducted a cross-sectional survey to investigate their drinking times, water consumption, and urine volumes at 0 min, 30 min, 60 min, 2 h, 24 h, and 48 h after radionuclide treatment. At each timepoint, their radiation dose equivalent rates were monitored at 0 m, 1 m, and 2 m from the middle abdomen. f at 24 h were significantly lower than those at 0 min, 30 min, 60 min, and 2 h (all p < 0.05). The dose equivalent rates at 48 h were significantly lower than those at 24 h (all p < 0.05). At 1 m or 2 m from the patient, the dose equivalent rate gradually decreased at all six timepoints and was significantly different between groups (P < 0.05). To achieve lower radiation doses, there was a correlation with 24 h water consumption (P < 0.05) but no correlation with 48 h water consumption (P > 0.05); there were lower peripheral dose equivalents for patients when 24 h water consumption was no less than 2,750 mL. Patients with neuroendocrine tumors should drink at least 2,750 mL of water 24 h after treatment with 177Lu-DOTATATE radionuclides. Drinking water in the first 24 h after treatment is more critical to reduce the peripheral dose equivalent, which can accelerate the reduction of peripheral radiation dose equivalent in early patients.

3.
Cancers (Basel) ; 15(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37190222

RESUMO

The majority of lung cancer patients are diagnosed with metastatic disease. This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). Based on association with patient survival (n = 1016), 10 miRNAs were identified as potential tumor suppressors (hsa-miR-144, hsa-miR-195, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-335, hsa-miR-363, hsa-miR-451, and hsa-miR-99a), and 4 were identified as potential oncogenes (hsa-miR-21, hsa-miR-31, hsa-miR-411, and hsa-miR-494) in lung cancer. Experimentally confirmed target genes were identified for the 73 diagnostic miRNAs, from which proliferation genes were selected from CRISPR-Cas9/RNA interference (RNAi) screening assays. Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. DGKE and WDR47 were found with significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. These findings have implications for improving lung cancer diagnosis, optimizing treatment selection, and discovering new drug options for better patient outcomes.

4.
Angew Chem Int Ed Engl ; : e202219062, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37186098

RESUMO

BN-butafulvenes, mono-BN isosteres of butafulvene and highly strained isomers of azaborines and B-amino boroles, have been synthesized via hydrolysis of the urana-borabicyclic complexes obtained from the reactions of bis(alkynyl)boranes with an uranacyclopropene complex. Their 4-dimethylaminopyridine (DMAP) adducts can further isomerize to 1,2,4,6-multisubstituted BN-9,1-naphthalenes. Both NMR reaction monitoring and theoretical calculations point to a reaction mechanism involving dearomative insertion of DMAP followed by two consecutive 1,2-hydrogen shifts. The photophysical studies of the highly substituted BN-9,1-naphthalenes reveal a notable redshift in both the UV-vis absorption and emission spectra. The (TD)-DFT calculations corroborate the experimental data, suggesting that the strong π-donating amino substitution at the 1- and/or 6-positions destabilizes the HOMO, and thus leading to a notable decrease of the HOMO-LUMO gap.

5.
Neuropsychologia ; : 108568, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37150438

RESUMO

Faces and Chinese characters are both objects of perceptual expertise. In this study, we investigated the characteristics of interhemispheric transmission times (IHTTs) in both transmission direction and transmission efficiency during the processing of objects of perceptual expertise. A total of 112 participants engaged in a divided visual field paradigm for faces, Chinese characters, and houses in both upright and inverted orientations. The N170 amplitudes elicited by the objects of perceptual expertise (faces and Chinese characters) involved in this study were larger than those elicited by the non-perceptual expertise objects (houses). We used the latencies of the N170 component of the event-related potential (ERP) recorded in the left and right hemispheres to calculate the IHTTs. For all objects, the N170-related IHTTs from the right to the left hemispheres were shorter than those in the opposite direction. Essentially, the N170-related IHTTs for faces were shorter, that is, more efficient than those for Chinese characters and houses. This result indicates that the IHTTs during perceptual expertise and non-perceptual expertise object processing share a common transmission direction advantage, but transmission efficiency is face-specific.

6.
Front Pediatr ; 11: 1155004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168807

RESUMO

Background: Previous studies have reported that the incidence of pediatric inflammatory bowel disease (IBD) is related to vitamin D, but it is still unclear. This study intends to calculate the relationship between pediatric IBD and vitamin D. Methods: A comprehensive literature search from inception to January 2023 was performed in the PubMed, EMBASE, Medline, Web of Science, and Google Scholar databases. Relevant data were extracted as required and used for subsequent calculations. Results: Sixteen papers were included, and there was no significant difference between the average vitamin D level in IBD patients and healthy controls. In addition, the overall pooled results showed that C-reactive protein (CRP) was 2.65 higher before vitamin D supplementation than after supplementation [SMD = 2.65, 95% CI = (2.26, 3.04)]. Moreover, patients with IBD in remission were 0.72 higher before vitamin D supplementation than after supplementation [OR = 0.72, 95% CI = (0.52, 1.00)]. Conclusion: This study suggested that there was no obvious relationship between pediatric IBD and vitamin D, while vitamin D supplementation can improve disease activity. Therefore, follow-up still needs many prospective studies to confirm the relationship between pediatric IBD and vitamin D.

7.
World J Gastrointest Surg ; 15(4): 600-620, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37206078

RESUMO

BACKGROUND: The incidence rate of acute pancreatitis (AP), which is a pathophysiological process with complex etiology, is increasing globally. miR-125b-5p, a bidirectional regulatory miRNA, is speculated to exhibit anti-tumor activity. However, exosome-derived miR-125b-5p in AP has not been reported. AIM: To elucidate the molecular mechanism of exosome-derived miR-125b-5p promoting AP exacerbation from the perspective of the interaction between immune cells and acinar cells. METHODS: Exosomes derived from AR42J cells were isolated and extracted in active and inactive states by an exosome extraction kit, and were verified via transmission electron microscopy, nanoparticle tracking analysis, and western blotting. RNA sequencing assay technology was used to screen differentially expressed miRNAs in active and inactive AR42J cell lines, and bioinformatics analysis was used to predict downstream target genes of miR-125b-5p. The expression level of miR-125b-5p and insulin-like growth factor 2 (IGF2) in the activated AR42J cell line and AP pancreatic tissue were detected by quantitative real-time polymerase chain reaction and western blots. The changes in the pancreatic inflammatory response in a rat AP model were detected by histopathological methods. Western Blot was used to detect the expression of IGF2, PI3K/AKT signaling pathway proteins, and apoptosis and necrosis related proteins. RESULTS: miR-125b-5p expression was upregulated in the activated AR42J cell line and AP pancreatic tissue, while that of IGF2 was downregulated. In vitro experiments confirmed that miR-125b-5p could promote the death of activated AR42J cells by inducing cell cycle arrest and apoptosis. In addition, miR-125b-5p was found to act on macrophages to promote M1 type polarization and inhibit M2 type polarization, resulting in a massive release of inflammatory factors and reactive oxygen species accumulation. Further research found that miR-125b-5p could inhibit the expression of IGF2 in the PI3K/AKT signaling pathway. Additionally, in vivo experiments revealed that miR-125b-5p can promote the progression of AP in a rat model. CONCLUSION: miR-125b-5p acts on IGF2 in the PI3K/AKT signaling pathway and promotes M1 type polarization and inhibits M2 type polarization of macrophage by inhibiting IGF2 expression, resulting in a large release of pro-inflammatory factors and an inflammatory cascade amplification effect, thus aggravating AP.

8.
Transp Res Rec ; 2677(3): 1551-1566, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37063707

RESUMO

This paper investigates the intellectual structure of the literature addressing "epidemic/pandemic" and "aviation industry" through a bibliometric approach to the literature from 1991 to 2021. The final count of 856 publications was collected from Web of Science and analyzed by CiteSpace (version 5.8.R1) and VOS Viewer. Visualization tools are used to perform the co-citation, co-occurrence, and thematic-based cluster analysis. The results highlight the most prominent nodes (articles, authors, journals, countries, and institutions) within the literature on "epidemic/pandemic" and "aviation industry." Furthermore, this study conceptualizes and compares the growth of literature before theCOVID-19 pandemic and during the COVID-19 ("hotspot") era. The conclusion is that the aviation industry is an engine for global economics on the road to recovery from COVID-19, in which soft (human) resources can play an integral part.

9.
Int J Ophthalmol ; 16(4): 547-553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077475

RESUMO

AIM: To observe the clinical efficacy of the combined use of small incision lenticule extraction (SMILE)-derived lenticule patches in corneal dermoid excision, with fixation of the lenticule patches assisted by fibrin glue. METHODS: Seventeen eyes of 17 patients with corneal dermoid were treated with dermoid removal combined with SMILE-derived lenticule transplantation. All lenticule patches were fixed by fibrin glue. Ocular changes were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography. The best-corrected visual acuity (BCVA) and ocular dioptric variations were examined preoperatively and postoperatively. Intraocular pressure (IOP) was also monitored in all visited time. RESULTS: Totally, 18 lenticule patches were used on 17 eyes of 17 cornea dermoid patients. The mean follow-up time was 11.47±5.28mo. All lenticule patches were successfully glued, kept on its location and maintained transparent during the follow-up time, with a consecutive epithelial cover for 1wk. Nine of the patients could coordinate visual and optometry exam well. Their preoperative BCVA is 0.60±0.35 in decimal, significantly improved to 0.80±0.26 in decimal at 6mo postoperatively (Z=-2.392, P=0.017), but the changes of their corneal astigmatism diopters showed no significance, with 2.22±1.91 D preoperatively, and 2.28±1.31 D at 6mo postoperatively (Z=-0.135, P=0.893). Limbal pannus formation occurred in 4 (23.52%) cases and decreased with the application of tacrolimus eyedrops. IOP increased in 2 (11.76%) cases, but well decreased by timolol maleate eyedrops. All the adult patients or guardians of minor patients were satisfied with the cosmetic improvement. CONCLUSION: Dermoid excision combined with transplantation of SMILE-derived lenticule patches using fibrin glue is a safe and effective novel tectonic keratoplasty procedure for corneal dermoid.

10.
Nanomaterials (Basel) ; 13(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37110996

RESUMO

The extraction of titanium-bearing components in the form of CaTiO3 is an efficient utilization of blast furnace slag. The photocatalytic performance of this obtained CaTiO3 (MM-CaTiO3) as a catalyst for methylene blue (MB) degradation was evaluated in this study. The analyses indicated that the MM-CaTiO3 had a completed structure with a special length-diameter ratio. Furthermore, the oxygen vacancy was easier to generate on a MM-CaTiO3(110) plane during the photocatalytic process, contributing to improving photocatalytic activity. Compared with traditional catalysts, MM-CaTiO3 has a narrower optical band gap and visible-light responsive performance. The degradation experiments further confirmed that the photocatalytic degradation efficiency of pollutants by using MM-CaTiO3 was 3.2 times that of pristine CaTiO3 in optimized conditions. Combined with molecular simulation, the degradation mechanism clarified that acridine of MB molecular was stepwise destroyed by using MM-CaTiO3 in short times, which is different from demethylation and methylenedioxy ring degradation by using TiO2. This study provided a promising routine for using solid waste to obtain catalysts with excellent photocatalytic activity and was found to be in keeping with sustainable environmental development.

11.
Phytochemistry ; 210: 113671, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37024001

RESUMO

Five undescribed dolabellane-type diterpenoids (1-5), together with three related known ones (6-8), were isolated from the soft coral Clavularia viridis. Their structures and stereochemistry were elucidated by extensive spectroscopic analysis and NMR calculation with DP4+ probability analysis. The absolute configurations of 1 and 5 were unambiguously determined by X-ray crystallographic analysis. A plausible biosynthetic connection between undescribed compounds 1-5 was proposed.


Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Estrutura Molecular , Diterpenos/química , Espectroscopia de Ressonância Magnética
12.
Brain Behav ; : e3014, 2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37062885

RESUMO

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

13.
Chemistry ; : e202301270, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37098696

RESUMO

In this contribution, we reported the three-dimensional (3D) analogues of N-heterocyclic carbene (NHC) stabilized 9-borafluorenium 3 and 9-borafluorene radical 4. The radical was fully characterized by NMR, cyclic voltammetry (CV), UV-Vis absorption, electron paramagnetic resonance (EPR) and single-crystal X-ray diffraction analyses. The distinct boron-centered radical character of 4 was corroborated by DFT calculations and EPR analysis.

14.
ACS Appl Mater Interfaces ; 15(15): 18878-18888, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37018000

RESUMO

The implementation of all-solid-state lithium batteries (ASSLBs) is regarded as an important step toward the next-generation energy storage systems. The sulfide solid-state electrolyte (SSE) is a promising candidate for ASSLBs due to its high ionic conductivity and easy processability. However, the interface stability of sulfide SSEs toward high-capacity cathodes like nickel-rich layered cathodes is limited by the interfacial side reaction and narrow electrochemical window of the electrolyte. Herein, we propose introducing the halide SSE Li3InCl6 (LIC) with high (electro)chemical stability and superior Li+ conductivity to act as an ionic conductive additive in the Ni-rich LiNi0.8Co0.1Mn0.1O2 (NCM) cathode mixture through a slurry coating, aiming to build a stable cathode-electrolyte interface. This work demonstrates that the sulfide SSE Li5.5PS4.5Cl1.5 (LPSCl) is chemically incompatible with the NCM cathode, and the indispensable role of the substitution of LPSCl with LIC in enhancing the interfacial compatibility and oxidation stability of the electrolyte is highlighted. Accordingly, this new configuration shows superior electrochemical performance at room temperature. It shows a high initial discharge capacity (136.3 mA h g-1 at 0.1C), cycling performance (77.4% capacity retention at the 100th cycle), and rate capability (79.3 mA h g-1 at 0.5C). This work paves the way for investigating interfacial challenges regarding high-voltage cathodes and provides new insights into possible interface engineering strategies.

15.
Nat Commun ; 14(1): 2188, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069185

RESUMO

Quantifying the stomatal responses of plants to global change factors is crucial for modeling terrestrial carbon and water cycles. Here we synthesize worldwide experimental data to show that stomatal conductance (gs) decreases with elevated carbon dioxide (CO2), warming, decreased precipitation, and tropospheric ozone pollution, but increases with increased precipitation and nitrogen (N) deposition. These responses vary with treatment magnitude, plant attributes (ambient gs, vegetation biomes, and plant functional types), and climate. All two-factor combinations (except warming + N deposition) significantly reduce gs, and their individual effects are commonly additive but tend to be antagonistic as the effect sizes increased. We further show that rising CO2 and warming would dominate the future change of plant gs across biomes. The results of our meta-analysis provide a foundation for understanding and predicting plant gs across biomes and guiding manipulative experiment designs in a real world where global change factors do not occur in isolation.


Assuntos
Dióxido de Carbono , Fotossíntese , Fotossíntese/fisiologia , Ecossistema , Clima , Plantas , Mudança Climática
16.
Stroke ; 54(4): 1088-1098, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36912142

RESUMO

BACKGROUND: Stroke is the primary cause of chronic disability in the elderly, as there are no neurorestorative treatments for those who do not qualify for recanalization therapy. Experimental evidence in stroke animals suggests that transplantation of bone marrow-derived human mesenchymal stem cells (hMSCs) holds promise, but hMSC transplantation has not been systematically tested in aged animals. We tested the hypothesis that poststroke hMSC transplantation improves stroke recovery in aged mice by promoting brain repair. METHODS: Permanent focal cerebral ischemia was induced in 20-month-old C57BL/6 male mice by distal middle cerebral artery occlusion. Bone marrow-derived hMSCs were expanded in vitro and then administrated intravenously into mice (1×106 cells in PBS) 24 hours after distal middle cerebral artery occlusion. Sensorimotor and cognitive functions, brain atrophy, and brain repair processes (neurogenesis, angiogenesis, oligodendrogenesis) were assessed for up to 56 days after stroke. RESULTS: Poststroke hMSC transplantation did not mitigate brain atrophy or improve neuronal survival at 56 days after distal middle cerebral artery occlusion. However, hMSC-treated mice displayed superior neurobehavioral performances in the open field, rotarod, adhesive removal, novel object, and Morris water maze tests compared with PBS-treated controls. hMSCs promoted white matter integrity and enhanced angiogenesis and oligodendrogenesis-but not neurogenesis-in the stroke brain. Positive correlations between neurobehavioral performance and brain repair profiles or white matter integrity were observed in stroke mice. CONCLUSIONS: Poststroke hMSC transplantation improves long-term stroke recovery in aged mice, likely via mechanisms involving enhanced microvascular regeneration and white matter restoration.


Assuntos
Isquemia Encefálica , Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Camundongos , Humanos , Masculino , Animais , Idoso , Lactente , Infarto da Artéria Cerebral Média/cirurgia , Camundongos Endogâmicos C57BL , Encéfalo , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/cirurgia , Modelos Animais de Doenças
17.
BMC Cancer ; 23(1): 270, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36964538

RESUMO

BACKGROUND: Since renal cell carcinoma(RCC) is insensitive to conventional chemoradiotherapy, molecularly targeted drugs are commonly used treatments for unresectable advanced RCC. The aim of this study was to explore the efficacy and safety of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced RCC. METHODS: This study included 98 patients with unresectable advanced RCC who were treated in Union Hospital from January 2015 to December 2018, and they met the criteria. They were divided into two groups: TACE + Sunitinib group (N = 47) and Sunitinib group (N = 51). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients. RESULTS: (1)TACE + Sunitinib group: 4 patients (8.5%) achieved CR, 27 patients (57.5%) achieved PR, 9 patients (19.1%) achieved SD, and 7 patients (14.9%) achieved PD. Sunitinib group, 0 patients (0%) achieved CR, 20 patients (39.2%) achieved PR, 14 patients (27.5%) achieved SD, and 17 patients (33.3%) achieved PD. (P = 0.017) (2)ORR: TACE + sunitinib group, 66.0%; sunitinib group, 39.2%. (P = 0.009) (3)DCR: TACE + sunitinib group, 85.1%; sunitinib group, 66.7%. (P = 0.038) (4) In the TACE + sunitinib group, mPFS was 15.6 months, mOS was 35.0 months; in the sunitinib group, the mPFS was 10.9 months, mOS was 25.7 months. (P < 0.001) (5) The incidence of abdominal pain, fever, and vomiting was higher in the TACE + sunitinib group than in the sunitinib group (abdominal pain: 55.3% vs. 13.7%; fever: 61.7% vs. 7.8%; vomiting: 40.4% vs. 19.6%; P < 0.05). The technical success rate of TACE in TACE + Sunitinib group is 100%. CONCLUSIONS: The TACE + sunitinib group had higher ORR and DCR, longer OS and PFS than the sunitinib alone group. TACE combined with sunitinib can play a complementary role and is a safe and effective treatment for advanced RCC.


Assuntos
Carcinoma Hepatocelular , Carcinoma de Células Renais , Quimioembolização Terapêutica , Neoplasias Renais , Neoplasias Hepáticas , Humanos , Sunitinibe/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Estudos Retrospectivos , Carcinoma Hepatocelular/terapia , Resultado do Tratamento , Neoplasias Hepáticas/terapia , Neoplasias Renais/tratamento farmacológico
19.
Int Immunopharmacol ; 117: 109614, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36878048

RESUMO

Cerebral amyloid angiopathy (CAA) is characterized by the cerebrovascular amyloid-ß (Aß) accumulation, and always accompanied by Alzheimer's disease (AD). Mitochondrial dysfunction-associated cellular events including cell death, inflammation and oxidative stress are implicated in the progression of CAA. Unfortunately, the molecular mechanisms revealing CAA pathogenesis are still obscure, thus requiring further studies. Mitochondrial calcium uptake 3 (MICU3), a regulator of the mitochondrial Ca2+ uniporter (MCU), mediates various biological functions, but its expression and influence on CAA are largely unknown. In the present study, we found that MICU3 expression was gradually declined in cortex and hippocampus of Tg-SwDI transgenic mice. Using stereotaxic operation with AAV9 encoding MICU3, we showed that AAV-MICU3 improved the behavioral performances and cerebral blood flow (CBF) in Tg-SwDI mice, along with markedly reduced Aß deposition through mediating Aß metabolism process. Importantly, we found that AAV-MICU3 remarkably improved neuronal death and mitigated glial activation and neuroinflammation in cortex and hippocampus of Tg-SwDI mice. Furthermore, excessive oxidative stress, mitochondrial impairment and dysfunction, decreased ATP and mitochondrial DNA (mtDNA) were detected in Tg-SwDI mice, while being considerably ameliorated upon MICU3 over-expression. More importantly, our in vitro experiments suggested that MICU3-attenuated neuronal death, activation of glial cells and oxidative stress were completely abrogated upon PTEN induced putative kinase 1 (PINK1) knockdown, indicating that PINK1 was required for MICU3 to perform its protective effects against CAA. Mechanistic experiment confirmed an interaction between MICU3 and PINK1. Together, these findings demonstrated that MICU3-PINK1 axis may serve as a key target for CAA treatment mainly through improving mitochondrial dysfunction.


Assuntos
Doença de Alzheimer , Angiopatia Amiloide Cerebral , Camundongos , Animais , Cálcio/metabolismo , Angiopatia Amiloide Cerebral/genética , Angiopatia Amiloide Cerebral/metabolismo , Angiopatia Amiloide Cerebral/patologia , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Inflamação/metabolismo , Neuroglia/metabolismo , Mitocôndrias/metabolismo , Proteínas Quinases/metabolismo , Encéfalo/metabolismo
20.
Ir J Med Sci ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36961673

RESUMO

BACKGROUND: The timely assessment of B-type natriuretic peptide (BNP) marking chronic heart failure risk in patients with coronary heart disease (CHD) helps to reduce patients' mortality. OBJECTIVE: To evaluate the potential of wrist pulse signals for use in the cardiac monitoring of patients with CHD. METHODS: A total of 419 patients with CHD were assigned to Group 1 (BNP < 95 pg/mL, n = 249), 2 (95 < BNP < 221 pg/mL, n = 85), and 3 (BNP > 221 pg/mL, n = 85) according to BNP levels. Wrist pulse signals were measured noninvasively. Both the time-domain method and multiscale entropy (MSE) method were used to extract pulse features. Decision tree (DT) and random forest (RF) algorithms were employed to construct models for classifying three groups, and the models' performance metrics were compared. RESULTS: The pulse features of the three groups differed significantly, suggesting different pathological states of the cardiovascular system in patients with CHD. Moreover, the RF models outperformed the DT models in performance metrics. Furthermore, the optimal RF model was that based on a dataset comprising both time-domain and MSE features, achieving accuracy, average precision, average recall, and average F1-score of 90.900%, 91.048%, 90.900%, and 90.897%, respectively. CONCLUSIONS: The wrist pulse detection technology employed in this study is useful for assessing the cardiac function of patients with CHD.

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